ArticleJournal of medicinal chemistry2016
Bifunctional Peptide-Based Opioid Agonist-Nociceptin Antagonist Ligands for Dual Treatment of Acute and Neuropathic Pain.
Article in Journal of medicinal chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
15 citing papers in PubMed, 48 citations in OpenAlex.
- Synthesis and Pharmacological Characterization of Nociceptin/Orphanin FQ Dimeric Ligands.Journal of medicinal chemistry · 2025Article
- Analgesic Peptides: From Natural Diversity to Rational Design.Molecules (Basel, Switzerland) · 2024Review
- Synthesis, Biological Activity and Molecular Docking of Chimeric Peptides Targeting Opioid and NOP Receptors.International journal of molecular sciences · 2022Article
- Bifunctional Opioid/Melanocortin Peptidomimetics for Use in Neuropathic Pain: Variation in the Type and Length of the Linker Connecting the Two Pharmacophores.International journal of molecular sciences · 2022Article
- Harnessing the Anti-Nociceptive Potential of NK2 and NK3 Ligands in the Design of New Multifunctional μ/δ-Opioid Agonist-Neurokinin Antagonist Peptidomimetics.Molecules (Basel, Switzerland) · 2021Article
- Comprehensive overview of biased pharmacology at the opioid receptors: biased ligands and bias factors.RSC medicinal chemistry · 2021Review
- Antinociceptive Efficacy of the µ-Opioid/Nociceptin Peptide-Based Hybrid KGNOP1 in Inflammatory Pain without Rewarding Effects in Mice: An Experimental Assessment and Molecular Docking.Molecules (Basel, Switzerland) · 2021Article
- Multifunctional Opioid-Derived Hybrids in Neuropathic Pain: Preclinical Evidence, Ideas and Challenges.Molecules (Basel, Switzerland) · 2020Review
- Optimized Opioid-Neurotensin Multitarget Peptides: From Design to Structure-Activity Relationship Studies.Journal of medicinal chemistry · 2020Article
- Crosstalk between Opioid and Anti-Opioid Systems: An Overview and Its Possible Therapeutic Significance.Biomolecules · 2020Review
- Antinociceptive and Cytotoxic Activity of Opioid Peptides with Hydrazone and Hydrazide Moieties at the C-Terminus.Molecules (Basel, Switzerland) · 2020Article
- Bidirectional Action of Cenicriviroc, a CCR2/CCR5 Antagonist, Results in Alleviation of Pain-Related Behaviors and Potentiation of Opioid Analgesia in Rats With Peripheral Neuropathy.Frontiers in immunology · 2020Article
- Impact of Botox-A SNAP-25 protein expression and the mechanism of inhibitory neurotransmitter imbalance in chronic sciatic nerve pain rat model.Experimental and therapeutic medicine · 2017Article
- Article
- Transmission pathways and mediators as the basis for clinical pharmacology of pain.Expert review of clinical pharmacology · 2016Article
Corrections and comments
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Authors and funding
19 authors at 10 institutions in 5 countries.
Funding
Abstract
Herein, the opioid pharmacophore H-Dmt-d-Arg-Aba-β-Ala-NH2 (7) was linked to peptide ligands for the nociceptin receptor. Combination of 7 and NOP ligands (e.g., H-Arg-Tyr-Tyr-Arg-Ile-Lys-NH2) led to binding affinities in the low nanomolar domain. In vitro, the hybrids behaved as agonists at the opioid receptors and antagonists at the nociceptin receptor. Intravenous administration of hybrid 13a (H-Dmt-d-Arg-Aba-β-Ala-Arg-Tyr-Tyr-Arg-Ile-Lys-NH2) to mice resulted in potent and long lasting antinociception in the tail-flick test, indicating that 13a was able to permeate the BBB. This was further supported by a cell-based BBB model. All hybrids alleviated allodynia and hyperalgesia in neuropathic pain models. Especially with respect to hyperalgesia, they showed to be more effective than the parent compounds. Hybrid 13a did not result in significant respiratory depression, in contrast to an equipotent analgesic dose of morphine. These hybrids hence represent a promising avenue toward analgesics for the dual treatment of acute and neuropathic pain.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.